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Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

In a randomized controlled trial that included 97 participants, 69% patients with Crohn’s disease (CD) allocated to a fasting-mimicking diet (FMD) achieved clinical response, and over 60% reached remission, outperforming the control group. The FMD also reduced markers of intestinal inflammation, suggesting this dietary intervention could serve as adjunctive treatment for CD.

The efficacy of an antidepressant is predicted from an EEG signature.

TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.

The authors introduce a deep learning framework to reproduce sequences of response times and use it to provide evidence for a stability–flexibility trade-off underlying task-switching costs.

Production of proteins at scale and affordable cost has been a major need of the biotech sector for the last several decades. Here the authors present a design algorithm called UNILIB for boosting gene expression in eukaryotic cells developed using an oligo-library and machine learning approach, validated in both yeast and mammalian cells using unseen sequences.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Leveraging genomic and epidemiological surveillance data, the authors show that flu epidemics in the US arise from independent outbreaks in different states that spread from state to state through commuting and compete for susceptible hosts.

Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.

While switch-like expression (“on” in some individuals and “off” in others) has been linked to biological variation and disease susceptibility, a systematic analysis across tissues is lacking. Here, we analyze genomes, transcriptomes, and methylomes from 943 individuals across 27 tissues, identifying 473 switch-like genes. The identified switch-like genes are enriched for associations with cancers and immune, metabolic, and skin diseases. Only 40 (8.5%) switch-like genes show genetically hardwired on-versus-off expression in all tissues analyzed, i.e., universally switch-like expression. The remaining switch-like genes show on versus off expression only in specific tissues. Methylation analysis suggests that genetically driven epigenetic silencing explains the universal pattern, whereas hormone-driven epigenetic modification may underlie tissue-specific switch-like gene expression. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, driven by tissue-specific master regulators. In the vagina, we identified seven concordantly switched off genes linked to vaginal atrophy. Experimental analysis of vaginal tissues shows that low estrogen levels lead to a decreased epithelial thickness and ALOX12 expression. We propose a model wherein switched off driver genes in basal and parabasal epithelia suppress cell proliferation, leading to epithelial thinning and vaginal atrophy. Our findings underscore the implications of switch-like genes for diagnostic and personalized therapeutic applications.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Functional connectivity estimates vary significantly across different functional magnetic resonance imaging preprocessing pipelines. Due to these variations, using seemingly similar minimal preprocessing does not ensure consistency.

Phage-coat proteins can be used to build synthetic biology parts. Here the authors use an oligo library and machine learning to predict and verify sequences based on binding scores.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.

Slide-tags enables multiomic sequencing of single cells and their localization within tissues.

Pancreatic cancer progression is driven by a switch from HNF4G-driven transcriptional activity in primary disease to FOXA1-mediated transcription in the metastatic setting.

The impacts of antimicrobial resistance are unequally distributed and are more severe in lower- and middle-income countries. Here, the authors perform a critical interpretive synthesis of the evidence on intersectional inequities driving antimicrobial resistance and present a conceptual framework of their findings.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

Assessing brain aging heterogeneity in a cohort of 49,482 individuals from 11 studies, a generative model identifies five dominant patterns of brain atrophy, with specific associations with biomedical, lifestyle and genetic factors.

The role of paddy rice agriculture in the spatial and temporal dynamics of atmospheric methane concentration remains unclear. Here, Zhang et al. show that regions with dense rice paddies have high satellite-based column averaged CH₄ concentrations (XCH₄), and that seasonal dynamics of XCH₄ mirror those of paddy rice growth.

Authors develop an integrated wireless system to examine brain states in freely-moving monkeys. They show that neural population activity in prefrontal cortex covaries with natural behavioral dynamics. Active behavior is associated with elevated arousal and increases in spiking activity while reducing low-frequency synchrony within cortical populations.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Using experimental and modelling evidence, this study reveals that small coral populations face fertilization failure due to Allee effects. The findings identify critical population thresholds needed to maintain reproductive success.

Gene expression is highly variable between tissues, and changes during development and with age. Here, the authors provide a comprehensive RNA-Seq analysis of the rat transcriptome, spanning eleven organs, four developmental stages and both sexes.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

The mechanistic link between cortical activity and behaviors remains largely unclear. Here authors show that targeted holographic photostimulation of mouse visual cortex during a detection task alters performance based on the animal’s state and visual stimulus conditions, highlighting the dynamic influence of cortical activity on perception and behavior.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

This study reveals the transition of move and evolve strategies and their interaction with niche opportunity and trait innovation throughout the diversification of the grape family—a globally distributed plant group originated in the Cretaceous.

Arrayed and pooled high-throughput screening is crucial for drug discovery and CRISPR functional genomics. Here, the authors present dFLASH; a dual FLuorescent transcription factor Activity Sensor for Histone-integrated live-cell reporting for high performance screening applications across numerous pathways and screening contexts.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Excised signal circles are circular DNA by-products of V(D)J recombination that form a complex with the V(D)J recombinase, and when increased in abundance, result in increased mutagenesis, causing adverse outcomes in cancer.

Tumour heterogeneity in clear cell renal cell carcinoma (ccRCC) remains to be investigated. Here, the integration of spatial omics, transcriptional and chromatin accessibility profiling at the single-nucleus level and bulk proteogenomics data reveal markers and pathways important for ccRCC.

Parkinson’s disease (PD) involves toxic protein buildup and energy failure in neurons. Continuously breathing low-oxygen air protected mice from PD-like neuronal loss and reversed symptoms, even after they began, suggesting that hypoxia may protect neurons.

Cells sense mechanical force through PIEZO1 channels. Here, authors show that both microgeometry and aspiration force mediate the PIEZO1 activity, and also alter F-actin organization, further amplifying PIEZO1 activity along membrane.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

This study provides a comprehensive analysis of small non-coding RNAs during human preimplantation development. It identifies key miRNA and snoRNA expression patterns, revealing their potential roles in blastocyst formation.

Bhatia et al. evaluate the ability of draining vein liquid biopsy to identify RAS-MEK pathway somatic genetic variants within children and young adults with extracranial arterio-venous malformations (AVMs). They demonstrate the effectiveness of using liquid biopsy to genotype extracranial AVMs in children.

Spectra decomposes gene expression data into interpretable programs using prior knowledge.

Visium spatial transcriptomics, single-nucleus RNA sequencing and co-detection by indexing are used to identify distinct spatial microregions in tumours and their microenvironment across six diverse solid cancer types.